Git 'r Dun

Really good news this week!

My neutrophils jumped from 1.29 last week all the way up to 1.70, and my liver enzymes dropped by more than 10%. The AST level is back to normal. Everything seems to be moving in the right direction, so I think I'll stick with the vitamin and chamomille cocktail I described in my previous post. I'm still doing the coffee/caffeine thing too.

As I write this post, I'm getting my 5th infusion of Rituxan. Prior to treatment, they drew blood for a FACS analysis to count the peripheral hairies, but I'm very confident they won't find any this time.

I'll add plots of the last 3 weeks' blood counts tonight, when I can get to a computer.

Here they are. As you can see most of the counts are back up to the levels they were at just prior to my first Rituxan treatment, when they had already peaked and had started to trend downward. Let's hope the upward momentum keeps going.

Boring is Good

Just finished my 4th cycle of Rituxan (gen. Rituximab), and it was extremely uneventful. Good thing too because I didn't take any Benadryl pre-meds this time. Infusion time was almost exactly three hours. This allowed me to stay alert, do some work on my iPhone, and now I'm about to go back to work at the office. Hopefully I can get 5 hours in before the day is done.

Basic dose information for me is as follows:
Total Dose: 803 mg
Concentration: 2 mg/mL
Dose Rate: initially at 50 mL/hr (100 mg/hr) increasing by 50 mL/hr every 15-30 minutes to 200 mL/hr (400 mg/hr).

The Rituxan total dose is calculated as follows:

My counts are pretty much holding steady for now, in a good range but not yet back up to remission levels. My liver enzymes crept up another 10 to 20%. It seems like nothing I do to make them better seems to work. I've read that people with Crohn's disease secrete high levels of TNFa and that TNFa is also a bone marrow suppressant. Perhaps other digestive issues such as gluten intolerance and Celiac also contribute to high TNFa levels independent of the presence of HCL. If so, then perhaps eliminating chamomile, vitamin A, vitamin E and Omega supplements in hopes of improving my liver function panel actually increased my residual TNFa levels and thus my liver enzymes too (the opposite effect of what I wanted). Then again, perhaps I'm just too impatient and overanalyze without enough data. I've asked for a cytokine panel, or at least a TNFa measurement, but have not heard back yet.

This week, I'm to going to take a vitamin D (1000 iu), E (200 iu) and an Omega-3-6-9 supplement twice daily (total 2000, 400 and 2) and drink chamomile three times a day to suppress TNFa and see if my counts go from holding steady to a pronounced improvement. I'll also take a daily multivitamin in the morning.

Overall it was a boring day, and boring is good.

The Vanishing Point

All I can say is Wow!

After one treatment with Rituxan, FACS results indicate that the percentage of hairy cells in my peripheral bloodstream plummeted from .4% to .05% -- a reduction of 87.5%! I can only hope that it's having the same effect on my marrow infiltration, but I believe it is.

I've now had 3 treatments with Rituxan, so one can expect that the percentage of hairies has now reduced to undectable levels with the standard FACS MRD detection technique. Blood for the next FACS will be taken prior to the Week 5 treatment, so we should know those results in about 3 weeks. It's likely the malignancy will be undetectable!

I also had my Pentamadine (lung antibiotic) treatment yesterday, and it went very well too. The taste was slightly bitter but tolerable. The Pentamadine is a nebulized once monthly treatment in lieu of Bactrim, to prevent the possibility of respiratory infection while being treated.

I'm still trying to figure out why my liver enzymes are elevated. I've been off Bactrim for 10 days, but my last chem20 panel indicated that both the AST and ALT liver enzyme levels went up slightly. I avoid all pain-killers except when they're required for my treatment. Gluten intolerance is also associated with tinnitus and elevated liver enzymes. I think the next step is to go strictly 100% gluten free -- pretty much live off fresh vegetables and meat all cooked at home for two weeks and see if the levels drop significantly.

Anyway, the good news is that the Rituxan is working very well. The FACS count after cycle 1 was .35 cells/uL. Assuming there are 6 liters of peripheral blood, this translates to approximately 2.1 million circulating hairy cells. This means the total HCL count went from 24 million down to 2.1 million in just 1 week.

If the kill process is arithmetic, and the kill capacity per cycle is only dependent on the available volume of Rituxan, then the second cycle may have already killed off the remaining circulating hairy cells; but if the reduction rate continues at 87% of the remaining cells per cycle, I'll still have a few circulating cells left in the near term after cycle 8 (the final cycle). As the cumulative concentration of Rituxan in my system continues its hairy cell search and destroy mission in the months that follow, the remaining cells should be annihilated.

Otherwise, if each round is only half as effective as the previous round, then the total peripheral load would be reduced by 95% in the short term after round 8, which is still really good, but may leave 10 to 20 thousand hairies remaining in the peripheral blood and possibly a hundred thousand or so in the marrow. That's why I need the hyper-sensitive MRD test.

Here's a semilog plot of the FACS cell count per micro-liter since I was diagnosed. If my estimates are correct, then at it's peak, I had 471 million circulating hairies. Now they're getting hard to count.



The treatments are going well. Let's hope all the cycles are as effective as the first one was!

I've got a lot to be thankful for this Thanksgiving!

Three down, five to go...

Rituxan, Week 2 -- Chimeric Boogaloo

I had my second cycle of Rituxan yesterday, and it went very well. I arrived at the NIH/NCI day hospital at 8 am, was lined up by 8:30, did the blood letting thing soon thereafter and had my Benadryl/Tylenol cocktail around 9:30 or so. We waited for the CBC results before starting my treatment at 10 am. It went very quickly, and since my body is now adjusted to Rituxan, I didn't need any Demerol this time. We started out at a rate of 50, then cranked it up to 200 half an hour later once my vitals checked out okay. I was done in 2 hours 45 minutes. A lot faster than the 7.5 hours it took the week before!

I got the pre-treatment CBC results before leaving and was very surprised by how quickly (and high) my platelets had rebounded. When I left 6 days earlier, my platelet count was at 88, but it jumped up to 122 by Monday morning. As you can see in the plot, that's the highest they've been since late May.



All the other counts had also risen significantly to near pre-Rituxan treatment levels. Two down, six to go...

11/18/2009 Update: Just got my pre-Rituxan flow report for the peripheral bloodstream. It indicates that the concentration of hairies in the peripheral bloodstream doubled to .4% from .2% just 1 week prior. Likewise, the count per microLiter also doubled, so the increase was consistent from both percentage and count perspectives. Given the decrease in normal counts that were also observed in the CBCs since remission was suggested, it's likely that my remission was going to just last a few months, if that. Looks like we hit the Rituxan just in time!

Of Mice and Men ...

I started Rituxan biotherapy on Monday in accordance with the NIH protocol. Rituxan is a chimeric monoclonal antibody. The Rituxan chimera is a hybrid of antibodies from both human and murine (mouse) antibodies. The CD20 antigen (a unique protein found on B-cells and abundantly on HCL mutant B-cells) is injected into a mouse, encouraging the production of antibodies. Antibody producing cells are then isolated from the spleen of the animal. These are then combined with immortal cells called myeloma cells. This results in a cell line that will go on producing the antibody indefinitely. Further genetic engineering removes the elements of the mouse cell that would normally produce an immune (allergic) reaction if injected into a human.

One of the forms describing the treatment actually said not to receive it if you have reactions to mouse proteins. How would anybody know that? Although there was that time I had rat-on-a-stick at the 1988 Seoul Olympics...

This is the 6-month post-chemo biotherapy to treat minimal residual disease (MRD). I was fortunate in that my tumor burden is very low, so not a lot of tumor lysis and subsequent reaction was to be expected; hence, less reaction than those with higher burdens in the peripheral blood and marrow. The percentage of hairies in my flow cytometry tests are .2% peripheral and 4% marrow (fairly minscule compared to people who rely on Rituxan as a first line treatment because they don't respond to Cladribine).

I was admitted as an in-patient on Sunday and treatment started on Monday morning. About 7:30 am, a phlebotomist came up to my room and drew blood for the pre-treatment CBC, chem20 and several other tests. Later in the morning, my IV line was placed. Even though I have good veins, they put an order in with the procedures unit to place my IV line using ultrasound. The nurse put the gel on my arm, swiped my arm, picked a vein and placed the line in under a minute. She was able to see the position of the catheter the entire time, so I didn't have to worry about it running into the side of a vein wall or valve. Nice!

My nurse, who was great, reviewed the purpose of the drug and possible side effects, the most common of which are chills, shakes and fever. Pre-meds included Benadryl and Tylenol and the initial Rituxan dosage rate was very low. The going in plan was 12.5 units (can't recall the precise unit label) steady for the first 4 hours, up it to 25 units at hour 4, then increase by 25 units every half hour after that unless reactions were seen. I was great the first hour, then I started to feel mild chills. I tried to fight it, but once I curled up under a blanket, I gave myself away and my nurse decided it was time to give me Demerol after a mild scolding for not telling her sooner. Demerol's a wonder narcotic for knocking out chills (among other things). I was fine after 15 minutes and after that, things went really well.

I took another Benadryl/Tylenol cocktail at hour 4. 10 minutes after each dosage increase, my temperature would go up (max'd at 38.6 C) but it would settle back down to the 37 to 37.5 range before the next increase. Vitals were taken every half hour prior to the dosage increases. Blood pressure was generally in the 118/69 range, pulse was normal and oxygen was anywhere from 95% to 98%. I finished the treatment in 7.5 hours.

I highly recommend that anyone receiving Rituxan biotherapy for HCL discuss Demerol as a option with their doctors. I think I would have suffered a lot without it and think it may help a lot of people who've generally just been treated with high doses of Benadryl. Dr. K is generally available to discuss his results and opinions. I'm sure he'd be happy to talk with your doctor.

I was discharged the next day and feel great, although my counts definitely took a dive. Even though Rituxan targets the CD20 proteins on B-cells, there is generally a broad spectrum affect on all blood counts (at least with the initial cycle) because the immune system goes into a hyper-drive response mode in the presence of the invading mouse protein component of the antibody. I assume the mechanism is some type of elevated phagocytosis but don't know for sure.

One week prior to the Rituxan treatment, I went in for my second bone marrow aspiration in as many weeks. With 4% hairies in the aspirate, I'm really hoping they can get the clone from this one so they can perform the patient specific hyper-sensitive MRD test in the future (1 cell in 1 million vice 1 cell in 10 thousand) when attacking the disease with Rituxan will have the best chance of eradicating it.

In other news, my liver enzyme tests have been consistently high for the past 3 months, so I'm starting to become more concerned. Tests for hepatitis antibodies have all been negative (thank goodness) so one possible remaining optionis that it's a temporary drug reaction caused by the Bactrim. I wrote to Dr. K asking if we could investigate other antibiotics, and he was very receptive and recommended a once-monthly inhaled drug in lieu of the Bactrim. We'll see if that returns the liver enzyme levels to normal.

Residual gluten in additives to the food I eat may be another factor contributing to the elevated liver enzyme levels. Many celiacs have very high liver enzyme levels prior to diagnosis as do people who are gluten intolerant. While I avoid gluten as much as possible, I'm not diligent in avoiding it all the time.

Interestingly enough, the product description for Bactrim also describes the fact that it sometimes has bone marrow suppressive effects, and I've seen anecdotal discussions that some patients have severe adverse reactions when they combine Bactrim and caffeine. Now I'm wondering if Bactrim was suppressing my marrow response after chemotherapy, and my recent experiments with caffeine to lower TNFa actually counter-acted a possible immune suppression effect Bactrim had on my marrow (I know, I know -- crazy mad-scientist and his theories). It'll be interesting to see if switching to the alternate antibiotic causes a dramatic acceleration in my future blood count responses.

Here're some plots of my most recent blood counts. Once again, my neutrophil count dropped when I reduced my coffee and chamomile intake in hopes of lowering my liver enzyme levels in preparation for the Rituxan therapy. Of course one day after Rituxan, everything took a nose dive, especially the lymphocytes. That's good, because the nasty hairies are part of the lymphocyte line of cells.

I've got seven cycles (1 per week) of Rituxan remaining. I'll keep you posted.

Miracles Happen!!!

Good news! I had a bone marrow biopsy (BMB) and blood tests on Monday and Dr. K says my critical blood counts are all above the minimum thresholds for remission (even if the platelets and neutrophils are below the low-end normal standards). For remission, they use a platelet count of 100K vice 160K. For neutrophils, they use 1.5 vice 1.73. Still, we must get the results of my flow cytometry to determine the level of malignant cells still in the peripheral bloodstream before we can say for sure that it's a complete remission (CR).

The percent infiltration in my marrow is now 30% -- down from a peak of 80% one month after chemo. This is great news, but the level of infiltration is still very high, and I wouldn't be surprised if I relapsed within 20 months. I want to do something about it -- take Rituxan and eradicate it. Unfortunately, I believe the presence of disease in the marrow is used as a control for comparative analysis, not as a qualification for determination of Minimal Residual Disease (MRD) and treatment with Rituxan.

MRD testing is still in its infancy and uses less invasive flow cytometry of peripheral blood in lieu of bone marrow biopsy. Flow cytometry of bone marrow aspirate (BMA) can also be performed, but that is invasive. The goal is to make bone marrow biopsies after the first chemotherapy treatment for Hairy Cell obsolete by developing reliable hyper-sensitive MRD tests along with some other proprietary techniques. Hence, if my flow test does not show MRD, treatment with Rituxan will wait until it does, even though we know there is still significant disease in the marrow. This means the number hairies in the marrow may increase, although they very well may continue to decrease at this point.

The truth is I want my flow to show MRD so I can zap the hairies in the marrow ASAP. If the hairies in the marrow are continuing to die off, then the Rituxan will accelerate the process. If they have already nadired and are on the way back up, then I definitely want to hit them while they're still down.

Now for the bad news. They want more bone marrow aspirate before they treat me with the Rituxan so I've got to go back in for another bone marrow aspiration. That'll be my fourth in the past 7 months. I'm anxious to do it though, because I think there's a good chance it will help a lot with evaluating MRD in the future.

Here's a plot showing a very dramatic increase in the number of neutrophils since last week:



The NCI threshold for remission is 1.5. As you can see, my neutrophils are now at their highest level since I've been collecting CBC data. I'm very relieved, but I'm ready to keep going.

I'll keep you posted.


Update: I just received the peripheral and BMA flow results. The percentage of hairies in the peripheral bloodstream is down to .2%. The percentage in the marrow aspirate is 4%. Thus, MRD has been detected at 6 months post-chemo. I'll go in for another BMA procedure on Monday. The current plan is to see if the BMA hairies will clone before starting Rituxan. This will take a week, so we'll hold off treatment until November 9th.

Live Hard

We've finally reached the 6 month post-chemo mark, and I'm feeling good. Since last month's post, I've had two CBCs and blood chemistry tests with some very interesting anecdotal evidence regarding caffeine and blood counts.

After my testing in August, I blogged about some research which indicated that caffeine can lower TNFa levels and hypothesized that since some research indicates that HCL apparently thrives on TNFa, maybe drinking coffee and consuming other TNFa lowering foods may improve or sustain my response.

The results from August to September were markedly improved. Upon seeing my liver function test results in September, I stopped taking the neurology drugs for my tinnitus and stopped drinking coffee and omega-3 supplements (fish oil has also been shown to lower TNFa). I was asked to come in two weeks later (September 29th) for a another blood sample so they could try to clone my hairies for PCR one last time before Rituxan treatments start, and they offered to do another CBC and chemistry as well (Nurse R went out of her way to arrange this for me). As shown in the plots below, my red counts, platelets and ANC all decreased in the two weeks between September 14th and September 29th, when I had ceased the coffee, chamomile tea and fish oil.

After getting the September 29th results, I decided to start taking the coffee, tea and fish oil supplements again before my next test, which was today. As you can see, there was improvement in all the counts from September 29th to October 23rd. Obviously this data is only anecdotal but nonetheless interesting in that it correlates with the presence of the anti-TNFa beverages and supplements.









Anyway, I'm now the proud owner of a Keurig single cup coffee brewer. I may even buy one for my office so I can avoid the battery acid that they try to pawn off as coffee. During the daytime, my co-workers know me as mild-mannered Mr. Coffee, not knowing my secret identity -- Java Man -- killer of hairy buggers everywhere (at least the ones in my bone marrow).

Tomorrow, I go in for my 6 month MRI, and my bone marrow biopsy (BMB) is scheduled for Monday, the 26th. Assuming it will take a week to get the pathology report, I expect to start Rituxan either Monday November 2nd, or the following Monday, November 9th. The first round will be administered over an 8 to 10 hour period, and I'll stay at the hospital overnight to make sure I don't have any adverse reactions. Many patients develop fever and vomit during the first round, but most respond with minimal side effects. After the first round, the time to administer subsequent rounds decreases to around 4 hours.

With respect to my daily activities, life is as normal as it's ever been. I haven't had a nose bleed in months, and even though my neutrophils are low, I still engage in pretty much all the activities I would have were I HCL-free. I try to bike 8 miles on Tuesday and Thursday and anywhere from 18 to 20 on Saturday. We've been to several county fairs and recently took Claire to a local Fall festival where we saw pigs and milking cows, rode slides and took a hay ride. I've added some pictures for everyone to enjoy.







Likewise, I'm pleased to announce that baby #2 is now on the way and doing very well -- just in time prior to starting the Rituxan. Once the Rituxan starts, natural conception must be avoided for at least 1 year. In the immortal words of Andy Dufresne: "Get busy living, or get busy dying." I choose to live hard.